How hydrogen sulfide coordinates glucose metabolism switch to promote cancer progression
The authors show that H2S promotes dissociation of PKM2 tetramer to monomer/dimer through protein sulfhydration (left). Inhibition of PKM2 activity results in the accumulation of metabolic intermediates required for the biosynthesis. Meanwhile, the PKM2 monomers or dimers translocate into the nucleus to facilitate multiple gene expressions to promote cancer progression.
The researchers also demonstrate that blockade of PKM2 sulfhydration at cysteine 326 by mutation stabilizes PKM2 tetramer to maintain high PK activity, resulting in high energy generation, low biosynthesis, and inhibition of tumor growth (right).
